Menu
GeneBe

15-101274445-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_018445.6(SELENOS):c.459G>A(p.Ser153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 1,609,026 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0091 ( 83 hom. )

Consequence

SELENOS
NM_018445.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.456
Variant links:
Genes affected
SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-101274445-C-T is Benign according to our data. Variant chr15-101274445-C-T is described in ClinVar as [Benign]. Clinvar id is 784687.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.456 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENOSNM_018445.6 linkuse as main transcriptc.459G>A p.Ser153= synonymous_variant 5/6 ENST00000526049.6
SELENOSNM_203472.3 linkuse as main transcriptc.459G>A p.Ser153= synonymous_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENOSENST00000526049.6 linkuse as main transcriptc.459G>A p.Ser153= synonymous_variant 5/61 NM_018445.6 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00593
AC:
903
AN:
152226
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00635
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00434
Gnomad FIN
AF:
0.00254
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00954
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00631
AC:
1521
AN:
240998
Hom.:
5
AF XY:
0.00643
AC XY:
838
AN XY:
130360
show subpopulations
Gnomad AFR exome
AF:
0.00247
Gnomad AMR exome
AF:
0.00593
Gnomad ASJ exome
AF:
0.00307
Gnomad EAS exome
AF:
0.000113
Gnomad SAS exome
AF:
0.00533
Gnomad FIN exome
AF:
0.00250
Gnomad NFE exome
AF:
0.00909
Gnomad OTH exome
AF:
0.00899
GnomAD4 exome
AF:
0.00915
AC:
13322
AN:
1456682
Hom.:
83
Cov.:
31
AF XY:
0.00905
AC XY:
6555
AN XY:
723940
show subpopulations
Gnomad4 AFR exome
AF:
0.00167
Gnomad4 AMR exome
AF:
0.00613
Gnomad4 ASJ exome
AF:
0.00312
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00529
Gnomad4 FIN exome
AF:
0.00312
Gnomad4 NFE exome
AF:
0.0106
Gnomad4 OTH exome
AF:
0.00798
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00592
AC:
902
AN:
152344
Hom.:
4
Cov.:
33
AF XY:
0.00502
AC XY:
374
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00190
Gnomad4 AMR
AF:
0.00634
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00435
Gnomad4 FIN
AF:
0.00254
Gnomad4 NFE
AF:
0.00954
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00777
Hom.:
0
Bravo
AF:
0.00650
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
2.3
Dann
Benign
0.67
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117645634; hg19: chr15-101814650; COSMIC: COSV101237247; COSMIC: COSV101237247; API